MK-801 and 7-Ni attenuate the activation of brain NF-κB induced by LPS
Abstract
The activation of nuclear factor-kappaB (NF-kappaB) leads to an increase in the expression of genes involved in important events in the central nervous system (CNS), such as development, plasticity and inflammation. It has been shown that inflammatory stimulus in the brain increases excitatory glutamatergic transmission, especially at N-methyl-D-aspartate (NMDA) receptor. These receptors have an important role in glutamate neurotoxicity and are in general coupled with the generation of nitric oxide (NO) through the activation of neuronal nitric oxide synthase (NOS). We have investigated the involvement of NMDA-NO pathway in LPS induction of NF-kappaB in CNS. Our results demonstrate that systemic LPS activates NF-kappaB in several regions of the CNS, which was partially reduced by the NMDA receptor antagonist dizolcipine (MK-801) and by the selective brain NOS inhibitor 7-Nitroindazol (7-Ni). 7-Ni effects were not synergic to MK-801 effects, suggesting that these compounds act through the same pathway. Dexamethasone caused a stronger reduction in LPS induction of NF-kappaB in CNS, demonstrating that MK-801 and 7-Ni act on a pathway that is responsible only by a fraction of the overall NF-kappaB activation. These results suggest that a considerable part of NF-kappaB activation by LPS is linked to the NMDA/NO pathway in CNS.
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Dexamethasone suppresses LPS-induced NF-kappaB activity in the murine brain.
“Glezer et al. have reported concordant results in vivo, by showing that dexamethasone suppresses LPS-induced NF-κB activity in the murine brain (133).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [133]
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- Authors
- Glezer, I., Munhoz, C. D., Kawamoto, E. M., Marcourakis, T., Avellar, M. C. W., & Scavone, C.
- Affiliations
- Universidade de São Paulo (BR)
- Universidade Federal de São Paulo (BR)
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 45
- Issue
- 8
- Pages
- 1120-1129
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2046571199
- Cited by
- 79
- References
- 49
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 2
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- NF-κB activation, lipopolysaccharide, MK-801, 7-nitroindazole, NMDA receptor, nitric oxide, neuronal nitric oxide synthase, neuroinflammation, brain, dexamethasone, glutamatergic neurotransmission
- MeSH terms
- Animals, Brain, Dose-Response Relationship, Drug, Indazoles, Lipopolysaccharides, Male, Dizocilpine Maleate, NF-kappa B, Rats, Wistar, Rats
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